Taek-Jong Hong

Gene–gene interaction between interleukin‐4 and interleukin‐4 receptor α in Korean children with asthma

Background Interleukin‐4 receptor α (IL‐4Rα), which binds IL‐4 and IL‐13, is involved in signal transduction of those cytokines that lead to IgE production, and is also a key functional component of the Th2 lymphocyte phenotype.

Gender Differences in Clinical Features and In-hospital Outcomes in ST-segment Elevation Acute Myocardial Infarction: From the Korean Acute Myocardial Infarction Registry (KAMIR) Study

Studies have suggested that women are biologically different and that female gender itself is independently associated with poor clinical outcome after an acute myocardial infarction (AMI).

TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the transcriptional and post-translational level in vascular smooth muscle cells

Despite extensive studies on cellular responses to activation of Toll-like receptor-4 (TLR-4), it is not evident weather its activation affects gene expression of interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs). Therefore, this study has investigated whether and how TLR-4 influences IL-8 expression in VSMCs. Exposure of aortic smooth muscle cells to TLR-4 agonistic lipopolysaccharide (LPS) not only enhanced release of IL-8 protein but also induced IL-8 gene transcript via promoter activation. The LPS-induced activation of IL-8 promoter was attenuated by dominant-negative MKK1, but not by dominant-negative MKK3. The promoter activation was also impaired by dominant negative CCAAT/enhancer binding protein (C/EBP), IkappaB, and dominant negative c-Jun. In comparison with the mutation of the AP-1 binding site, the mutation of NF-kappaB site and C/EBP binding site in the IL-8 promoter region more significantly impaired the promoter activation. Moreover, both promoter activity and release of IL-8 were inhibited by U0126 and curcumin, but not by SB202190, epigallocatechin 3-gallate and resveratrol. The present study reports that TLR-4-agonistic LPS upregulates IL-8 at the transcriptional and post-translational level in VSMCs, and that ERK1/2, NF-kappaB, and C/EBP play major roles in the upregulation of IL-8.

Different IL‐5 and IFN‐γ Production from Peripheral Blood T‐Cell Subsets in Atopic and Nonatopic Asthmatic Children

Defective Th1 and enhanced Th2‐type cytokine responses have been implicated in the development of atopic disease. However, the immunopathology of nonatopic asthma, especially in children, remains unclear, and there have been few studies to compare the cytokine profile in peripheral blood T‐cell subsets between atopic and nonatopic asthmatic children. To document whether atopic asthmatic children have a cytokine imbalance and to compare the cytokine profile between atopic and nonatopic asthmatic children, we investigated the interleukin (IL)‐5‐producing and interferon (IFN)‐γ‐producing T‐cell subsets from peripheral blood mononuclear cells (PBMC). The percentages of IFN‐γ‐producing CD4+ and CD8+ T cells from atopic asthmatic children were decreased, but those in nonatopic asthmatic children were not decreased. In both groups of asthmatic children, the percentages of IFN‐γ‐producing CD4+ T cells were inversely correlated with the peripheral blood eosinophils and had a significant correlation with airway responsiveness (PC20). Thus, we found that the mechanism underlying allergic inflammation of nonatopic asthma is not simple a Th1/Th2 cytokine imbalance. Considering the inverse relationship between IFN‐γ‐producing CD4+ T cells and eosinophilia or airway hyperresponsiveness, IFN‐γ from CD4+ T cells may play an important role in allergic inflammation and airway hyperresponsiveness in asthmatic children.

Assessment of the Efficacy and Tolerability of 2 Formulations of Atorvastatin in Korean Adults With Hypercholesterolemia: A Multicenter, Prospective, Open-Label, Randomized Trial

BACKGROUND A manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia. OBJECTIVE The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea. METHODS Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal. RESULTS A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88). CONCLUSIONS There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia.

Evaluation of the Dose-Response Relationship of Amlodipine and Losartan Combination in Patients with Essential Hypertension

BackgroundDespite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients.ObjectiveThe aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension.MethodsThis was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18–75 years with essential hypertension. At screening, patients received placebo for 2–4 weeks. Eligible patients (n = 320) were randomized to one of eight treatment groups: amlodipine 5 mg or 10 mg, losartan 50 mg or 100 mg, amlodipine camsylate/losartan 5 mg/50 mg, 5 mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg.Main Outcome MeasuresThe assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events.ResultsThe reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100 mg versus amlodipine 10mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant.ConclusionCombination amlodipine camsylate/losartan (5 mg/50 mg, 5 mg/100 mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension.Clinical Trial RegistrationRegistered at clinicaltrials.gov: NCT00942344.

Six-Month Versus 12-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents

Background— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P =0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P =0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P =0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P =0.005) among diabetic patients. Conclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration— URL: . Unique identifier: [NCT00698607][1]. # Clinical Perspective {#article-title-31} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00698607&atom=%2Fcirculationaha%2F125%2F3%2F505.atomBackground— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P=0.005) among diabetic patients. Conclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

Effects of high occupational physical activity, aging, and exercise on heart rate variability among male workers

ObjectivesEffects of aging and leisure time physical activity (LPA) might influence the effect of occupational physical activity (OPA) on risk for cardiovascular disease (CVD). This study was conducted to determine whether OPA affects CVD after controlling the effects of LPA and other risk factors for CVD such as job stress.MethodsParticipants were 131 male Korean manual workers. Tests for heart rate variability (HRV) were conducted for five minutes in the morning at work. We defined OPA as the combined concept of relative heart rate ratio (RHR), evaluated using a heart rate monitor.ResultsWhereas high OPA was not related to any HRV items in the younger age group, high OPA was associated with an increased number of low-value cases among all HRV items in older workers. Exercise had beneficial effects only in the younger group. After controlling for exercise and other risk factors, the odds ratios of the root-mean square of the difference of successive normal R-R intervals (rMSSD) and high frequency band power (HF) among the older age and high OPA group compared with the younger age and low OPA group were 64.0 and 18.5, respectively. Social support and shift work were independent risk factors in HRV.ConclusionsOPA in aging workers increases CVD risks. This study provides support for the need for protection of aging workers from physical work overload, and indicates the need for further study of optimal limits of OPA.

The impact of dose of the angiotensin-receptor blocker valsartan on the post-myocardial infarction ventricular remodeling: study protocol for a randomized controlled trial

BackgroundAngiotensin-converting enzyme inhibitors and the angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI). Based on previous clinical trials, a maximum clinical dose is recommended in practical guidelines. Yet, has not been clearly demonstrated whether the recommended dose is more efficacious compared to the lower dose that is commonly used in clinical practice.Method/DesignValsartan in post-MI remodeling (VALID) is a randomized, open-label, single-blinded multicenter study designed to compare the efficacy of different clinical dose of valsartan on the post-MI ventricular remodeling. This study also aims to assess neurohormone change and clinical parameters of patients during the post-infarct period. A total of 1116 patients with left ventricular dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to a maximal tolerable dose (up to 320 mg/day) or usual dose (80 mg/day) of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling is to be conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times.DiscussionVALID is a multicenter collaborative study to evaluate the impact of dose of valsartan on the post-MI ventricular remodeling. The results of the study provide information about optimal dosing of the drug in the management of patients after MI. The results will be available by 2012.Trial registrationNCT01340326

Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study

Purpose To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy. Patients and methods Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2.5/40 mg (n=63), CKD-828 2.5/80 mg (n=63), or S-amlodipine 2.5 mg (n=61) for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings. Results After the 8-week treatment, changes in sitDBP/systolic BP (SBP) were −9.67±6.50/−12.89±11.78, −10.72±6.19/−13.79±9.41, and −4.93±7.26/−4.55±11.27 mmHg in the CKD-828 2.5/40 mg (P<0.0001/P<0.0001), CKD-828 2.5/80 mg (P<0.0001/P<0.0001), and S-amlodipine 2.5 mg (P<0.0001/P=0.0027) groups, respectively, which were all significant BP reductions. At Week 8, the CKD-828 2.5/40 mg (sitDBP/SBP: P=0.0002/P<0.0001) and CKD-828 2.5/80 mg (sitDBP/SBP: P=0.0001/P<0.0001) showed superior BP-lowering effects to S-amlodipine 2.5 mg (P<0.001). At Week 4, all groups showed significant antihypertensive effects but both CKD-828 combinations (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) exhibited superior BP-lowering effects to that of S-amlodipine 2.5 mg (sitDBP/SBP: P=0.0028/P=0.0001 and P<0.0001/P=0.0012, respectively). The adverse event incidence was significantly lower in the CKD-828 2.5/40 mg (9.52%, P=0.0086) than in the S-amlodipine 2.5 mg group (27.87%) and increasing the telmisartan dose induced no unexpected adverse events, suggesting the safety of CKD-828. Conclusion CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy.